This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Alzheimer's disease (AD) is one of a number of age-related neurodegenerative diseases. The cause is unknown, but patients often present with brain pathology of plaques and tangles and, even more importantly, cell death. Vascular defects have been linked to AD development. For example, elderly patients who have undergone a stroke or ischemic episode are 2 times more likely to develop AD than patients who have not. The effects of reduced blood flow on the main pathological peptide in the AD brain, amyloid beta (A[unreadable]), has been documented in vitro and been linked to increased production. However, little is known about the vascular reactivity in AD, a more subtle defect which could contribute to cell death as the AD brain struggles to compensate for hypoxic episodes. In this work we employ spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) for non-contact intrinsic signal in vivo optical imaging of brain tissue composition and function. In SFDI, intrinsic chromophore concentrations of oxy- and deoxy-hemoglobin, water, and lipid, in addition to high-contrast wavelength-dependent maps of tissue scattering were recovered. Concurrent LSI acquisition yields average blood flow measurements. Together with inhaled gas challenges we measured baseline and dynamic changes in blood chromophore concentrations, blood flow, and brain tissue scattering in the AD triple transgenic and APP-/- mice.